Pollare T, Lithell H, Berne C
Department of Geriatrics, Uppsala University, Sweden.
N Engl J Med. 1989 Sep 28;321(13):868-73. doi: 10.1056/NEJM198909283211305.
It has been suggested that the metabolic side effects of antihypertensive drugs are responsible for their failure to reduce cardiovascular morbidity in patients with hypertension. Therefore, in 50 patients with essential hypertension, we performed a randomized, double-blind, crossover study comparing the effects of carbohydrate and lipid metabolism of captopril (mean [+/- SD] dose, 81 +/- 24 mg per day) and hydrochlorothiazide (40 +/- 12 mg per day) over two four-month treatment periods. Captopril increased the insulin-mediated disposal of glucose, as compared with placebo, from 5.7 +/- 2.4 to 6.3 +/- 2.5 mg per kilogram of body weight per minute (P less than 0.05), whereas hydrochlorothiazide caused a decrease from 6.4 +/- 2.0 to 5.7 +/- 1.9 (P less than 0.01). Captopril had no effect on the basal insulin concentration, but it decreased the late (30- to 90-minute) insulin response to glucose and increased the early (2- to 6-minute) insulin peak. Hydrochlorothiazide increased the basal insulin concentration and the late insulin response to glucose. These findings may be explained by an increase in insulin sensitivity with captopril and a decrease with hydrochlorothiazide. Little or no change was seen in serum lipid or lipoprotein levels during treatment with captopril, whereas hydrochlorothiazide caused significant increases in serum total (5 percent) and low-density lipoprotein (6 percent) cholesterol levels and total (15 percent) and very-low-density lipoprotein (25 percent) triglyceride levels, as compared with placebo (P less than 0.01 for all comparisons). We conclude that hydrochlorothiazide for the treatment of essential hypertension has adverse effects on glucose and lipid metabolism. It is possible, but not proved in this study, that these changes may contribute to the risk for diabetes mellitus and coronary heart disease. In contrast, captopril appears to have beneficial or no effects on glucose and lipid metabolism.
有人提出，抗高血压药物的代谢副作用是其未能降低高血压患者心血管发病率的原因。因此，我们对50例原发性高血压患者进行了一项随机、双盲、交叉研究，比较卡托普利（平均[±标准差]剂量，每天81±24毫克）和氢氯噻嗪（每天40±12毫克）在两个为期四个月的治疗期内对碳水化合物和脂质代谢的影响。与安慰剂相比，卡托普利使胰岛素介导的葡萄糖处置量从每分钟每公斤体重5.7±2.4毫克增加到6.3±2.5毫克（P<0.05），而氢氯噻嗪则使其从6.4±2.0毫克降至5.7±1.9毫克（P<0.01）。卡托普利对基础胰岛素浓度无影响，但它降低了对葡萄糖的晚期（30至90分钟）胰岛素反应，并增加了早期（2至6分钟）胰岛素峰值。氢氯噻嗪增加了基础胰岛素浓度和对葡萄糖的晚期胰岛素反应。这些发现可能是由于卡托普利使胰岛素敏感性增加，而氢氯噻嗪使其降低。在使用卡托普利治疗期间，血清脂质或脂蛋白水平几乎没有变化，而与安慰剂相比，氢氯噻嗪使血清总胆固醇（5%）和低密度脂蛋白胆固醇（6%）水平以及总甘油三酯（15%）和极低密度脂蛋白甘油三酯（25%）水平显著升高（所有比较P<0.01）。我们得出结论，用于治疗原发性高血压的氢氯噻嗪对葡萄糖和脂质代谢有不良影响。在本研究中，这些变化可能导致糖尿病和冠心病风险增加，但尚未得到证实。相比之下，卡托普利似乎对葡萄糖和脂质代谢有益或无影响。
